We will search for means to isolate and purify the angiotensin converting enzyme by affinity chromatography. We will compare various starting materials such as rabbit lung fresh tissue and acetone powder. We will study sandwich type affinity columns using double-headed inhibitors. We will study the specificity of the enzyme toward naturally occurring oligopeptides such as the enkephalins and establish if the activity detected in brain tissue is due to converting enzyme or something else. Since this enzyme normally acts while membrane bound, we will examine its properties in artifical vesicles and in isolated endothelial cell membranes. We will continue to investigate the nature of the metal binding site of converting enzyme by determining the stability constants for different metalloderivatives and measuring rates of metal association and dissociation versus pH. This will provide information about the amino acid side chains that are involved in metal binding. We will search for new inhibitors based on metal-chelation mechanisms in order to identify a specific, degradation-resistant agent with high affinity. Phosphoramidates will be given prominent attention.